This is aimed at studying further the structural details of the membranes forming low resistance junctions between cells of normal and neoplastic tissues, in an attempt to establish more precise structure-function correlations. A portionof the project is based on the hypothesis that variations in the arrangement of a certain globular structures seen in membranes of crayfish axo-axonal junctions are paralleled by changes in membrane resistance. Indeed preliminary experiments indicate that the uncoupling of adjacent cells in crayfish nervous system and rat stomach is paralleled by a closer packing of the intramembrane globules. The uncoupling is produced by incubation of the tissues in Ca ions chelators or metabolic inhibitors and is monitored in crayfish, by measuring intracullularly the increase in junctional resistance. In addition attempts will be made to isolate a pure fractionof vertebrate gap junctions and modify in vitro the pattern periodicity in order to study possible changes in the conformation of the junctional macromolecules and their dependence on divalent cations. The information to be obtained will include number, size, shape, and organization of the subunits composing each globular unit in the patterns and possibly the presence of presumed filaments bridging adjacent globules. The findings will allow one to test a hypothetical model proposed to explain the plasticity properties of the structures forming the junctional membranes. Other studies will be aimed at learning whether or not changes in the fine structures of the globular arrays are detectable in membranes of low resistance junctions between malignant cells versus those between normal cells. For this purpose the structure of junctions between electrically coupled cells from neoplastic tissues growing in vitro or in vivo will be studied by the various morphological methods.